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Humanization of Camelid Single-Domain Antibodies

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Single-Domain Antibodies

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2446))

Abstract

Humanization of therapeutic antibodies derived from animal immunizations is often required to minimize immunogenicity risks in humans, which can cause potentially harmful and serious side effects and reduce antibody efficacy. Humanization is typically applied to conventional monoclonal antibodies derived in rodents as well as single-domain antibodies isolated from camelids and sharks (VHHs and VNARs). A streamlined protocol is described here for sequence humanization of camelid VHHs, which represent a promising biotherapeutic format with many desirable attributes. From human framework selection and complementarity-determining region grafting strategies to empirical scoring for prioritization of back-mutations, step-by-step instructions, and templates are provided along with bioinformatics resources to assist each step of the humanization process. Alternative approaches, warnings, and caveats are also presented.

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Author information

Authors and Affiliations

  1. Human Health Therapeutics Research Centre, National Research Council Canada, Montreal, QC, Canada

    Traian Sulea

  2. Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, QC, Canada

    Traian Sulea

Authors
  1. Traian Sulea
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Correspondence to Traian Sulea .

Editor information

Editors and Affiliations

  1. Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON, Canada

    Greg Hussack

  2. Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON, Canada

    Kevin A. Henry

1 Electronic Supplementary Material

Data 1

PyMOL session file (.pse) of the 3D structural model depicted in Fig. 2b. Editable formats of the figures are also made available. (PSE 266 kb)

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© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Sulea, T. (2022). Humanization of Camelid Single-Domain Antibodies. In: Hussack, G., Henry, K.A. (eds) Single-Domain Antibodies. Methods in Molecular Biology, vol 2446. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2075-5_14

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  • DOI: https://doi.org/10.1007/978-1-0716-2075-5_14

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2074-8

  • Online ISBN: 978-1-0716-2075-5

  • eBook Packages: Springer Protocols

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